“Chemoprevention” with Nicotinamide- Valiant Efforts to Prevent Skin Cancer Development.

Our post will discuss a recent article was published in this week’s issue of the New England Journal of Medicine.

Keratinocyte carcinomas, including basal-cell carcinoma and squamous-cell carcinoma of the skin, are the most common cancers in humans with an annual incidence greater than all other cancers combined. While sun-protective techniques remain the most effective mitigation strategy, inconsistent implementation results in a considerable health problem, especially in high-risk groups such as persons with compromised immune systems.

Chemoprophylactic approaches have provided mixed results, but the administration of nicotinamide, the amide form of vitamin B3, has been shown to lower the rate of new nonmelanoma skin cancers by nearly 25% among patients with competent immune systems. Unfortunately, solid-organ transplant patients have a greatly increased risk of nonmelanoma skin cancer, and while the use of chemoprevention with oral retinoids has been recommended, their uptake in routine clinical practice has varied.

In my experience, their tumors nearly always display high-risk features under the microscope, and when completely extirpated, have larger defects to reconstruct.

Given the favorable side-effect profile of nicotinamide, coupled with the results seen in immune-competent patients, this therapy is routinely recommended in high-risk patients. However, data from randomized trials assessing the clinical usefulness of nicotinamide in solid-organ transplant recipients are limited, and the ONTRANS trial showed that nicotinamide lacks clinical usefulness in preventing the development of keratinocyte carcinomas in solid-organ transplant recipients.

The disappointing result really showed the limitations of generalizing results across various subpopulations of patients and promotes a need for additional approaches to help improve outcomes in our most at-risk populations. Emphasizing the importance of lifelong sun-protective practices for persons with sun-sensitive phenotypes is imperative in reducing pretransplantation risk. Immunopreventive strategies with immune checkpoint inhibitors before transplantation in the highest-risk patients have yet to be explored; nevertheless, given the activity of immunotherapy in nonmelanoma skin cancers, such approaches should be thoughtfully considered. The goal remains to minimize risk factors before transplantation and to mitigate the development of keratinocyte carcinomas after transplantation continues.

In my practice, I always take my time and adopt a meticulous approach towards transplant patients. I try to remove more than I initially would, and triple check my margins with tissue processing techniques and a colleague in pathology. However, the work is never completely over. Chemoprevention strategies are always discussed with their medical oncologist or physician who prescribes the immunosuppressive medications. My goal is to contribute and develop post-surgical, multi-disciplinary processes to aid the patient from the development of future skin cancers.